{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:00:38Z","timestamp":1791424838158,"version":"4.3.3"},"reference-count":95,"publisher":"Cold Spring Harbor Laboratory","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genome Res."],"published-print":{"date-parts":[[1996,11]]},"abstract":"<jats:p>Over 100 distinct disease-associated mutations have been identified in the breast-ovarian cancer susceptibility gene BRCA1. Loss of the wild-type allele in &gt; 90% of tumors from patients with inherited BRCA1 mutations indicates tumor suppressive function. The low incidence of somatic mutations suggests that BRCA1 inactivation in sporadic tumors occurs by alternative mechanisms, such as interstitial chromosomal deletion or reduced transcription. To identify possible features of the BRCA1 genomic region that may contribute to chromosomal instability as well as potential transcriptional regulatory elements, a 117,143-bp DNA sequence encompassing BRCA1 was obtained by random sequencing of four cosmids identified from a human chromosome 17 specific library. The 24 exons of BRCA1 span an 81-kb region that has an unusually high density of Alu repetitive DNA (41.5%), but relatively low density (4.8%) of other repetitive sequences. BRCA1 intron lengths range in size from 403 bp to 9.2 kb and contain the intragenic microsatellite markers D17S1323, D17S1322, and D17S855, which localize to introns 12, 19, and 20, respectively. In addition to BRCA1, the contig contains two complete genes: Rho7, a member of the rho family of GTP binding proteins, and VAT1, an abundant membrane protein of cholinergic synaptic vesicles. Partial sequences of the 1A1-3B B-box protein pseudogene and IFP 35, an interferon induced leucine zipper protein, reside within the contig. An L21 ribosomal protein pseudogene is embedded in BRCA1 intron 13. The order of genes on the chromosome is: centromere-1FP 35-VAT1-Rho7-BRCA1-1A1-3B-telomere.<\/jats:p>","DOI":"10.1101\/gr.6.11.1029","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:18:07Z","timestamp":1181078287000},"page":"1029-1049","source":"Crossref","is-referenced-by-count":215,"title":["Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1."],"prefix":"10.1101","volume":"6","author":[{"given":"T M","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M K","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C I","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Jerome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"McEuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Hood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M C","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1996,11,1]]},"reference":[{"key":"2021111810261540000_6.11.1029.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0894-472"},{"key":"2021111810261540000_6.11.1029.2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1990.9999"},{"key":"2021111810261540000_6.11.1029.3","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1381"},{"key":"2021111810261540000_6.11.1029.4","first-page":"229","article-title":"Transcription from TATA-less promoters: Dihydrofolate reductase as a model.","volume":"3","year":"1993","journal-title":"Crit. Rev. Eukaryotic Gene Exp."},{"key":"2021111810261540000_6.11.1029.5","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0021-9258(17)42225-3","article-title":"IFP 35 is an interferon-induced leucine zipper protein that undergoes interferon-regulated cellular redistribution.","volume":"269","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2021111810261540000_6.11.1029.6","doi-asserted-by":"publisher","DOI":"10.1007\/BF00163204"},{"key":"2021111810261540000_6.11.1029.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.1.1"},{"key":"2021111810261540000_6.11.1029.8","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(90)90190-6"},{"key":"2021111810261540000_6.11.1029.9","first-page":"2507","article-title":"The 5\u2032 end of the BRCA1 gene lies within a duplicated region of human chromosome 17q21.","volume":"12","year":"1996","journal-title":"Oncogene"},{"key":"2021111810261540000_6.11.1029.10","doi-asserted-by":"publisher","DOI":"10.1038\/372733a0"},{"key":"2021111810261540000_6.11.1029.11","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.4.589"},{"key":"2021111810261540000_6.11.1029.12","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-387"},{"key":"2021111810261540000_6.11.1029.13","first-page":"117","article-title":"Small GTP-binding proteins of the ras family: A conserved functional mechanism?","volume":"3","year":"1991","journal-title":"Cancer Cells"},{"key":"2021111810261540000_6.11.1029.14","first-page":"195","article-title":"Phl+bcr_ acute leukemias: Implications of Alu sequences in a chromosomal translocation occurring in the new cluster region within the BCR gene.","volume":"4","year":"1989","journal-title":"Oncogene"},{"key":"2021111810261540000_6.11.1029.15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.19.7631"},{"key":"2021111810261540000_6.11.1029.16","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1008"},{"key":"2021111810261540000_6.11.1029.17","first-page":"2393","article-title":"Human epithelial ovarian cancer allelotype.","volume":"53","year":"1993","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380080102"},{"key":"2021111810261540000_6.11.1029.19","first-page":"5617","article-title":"Identification of three regions on chromosome 17q in primary human breast carcinomas which are frequently deleted.","volume":"53","year":"1993","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.20","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-236"},{"key":"2021111810261540000_6.11.1029.21","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90072-6"},{"key":"2021111810261540000_6.11.1029.22","unstructured":"Deininger, P.L. 1989. SINEs: Short interspersed repeated DNA in higher eukaryotes. In Mobile DNA (ed. M. Howe and D. Berg), p. 972. American Society for Microbiology, Washington, D.C."},{"key":"2021111810261540000_6.11.1029.23","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(76)90264-3"},{"key":"2021111810261540000_6.11.1029.24","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.6.835"},{"key":"2021111810261540000_6.11.1029.25","first-page":"678","article-title":"Genetic linkage analysis in familial breast and ovarian cancer: Results from 214 families.","volume":"52","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199601183340302"},{"key":"2021111810261540000_6.11.1029.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91578-4"},{"key":"2021111810261540000_6.11.1029.28","first-page":"6374","article-title":"The search for BRCA1.","volume":"54","year":"1994","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.29","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-399"},{"key":"2021111810261540000_6.11.1029.30","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(95)80133-7"},{"key":"2021111810261540000_6.11.1029.31","first-page":"1284","article-title":"Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.","volume":"57","year":"1995","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.32","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939630"},{"key":"2021111810261540000_6.11.1029.33","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-428"},{"key":"2021111810261540000_6.11.1029.34","first-page":"451","article-title":"Rapid detection of regionally clustered germ-line BRCA1 mutations by multiplex heteroduplex analysis.","volume":"58","author":"U.F.O.C.S. Group.","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.35","unstructured":"Genetics Computer Group, Inc. 1994. the Wisconsin Sequence Analysis Package, Version 8.0. Madison, WI."},{"key":"2021111810261540000_6.11.1029.36","first-page":"2130","article-title":"Deletions and insertions in the p53 tumor suppressor gene in human cancers: Confirmation of the DNA polymerase slippage\/misalignment model.","volume":"56","year":"1996","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.37","first-page":"717","article-title":"Cell cycle regulation of BRCA1 messenger RNA in human breast epithelial cells.","volume":"7","year":"1996","journal-title":"Cell Growth Diff."},{"key":"2021111810261540000_6.11.1029.38","first-page":"4561","article-title":"Hormone-dependent regulation of BRCA1 in human breast cancer cells.","volume":"55","year":"1995","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.2270482"},{"key":"2021111810261540000_6.11.1029.40","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.8.1259"},{"key":"2021111810261540000_6.11.1029.41","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1654"},{"key":"2021111810261540000_6.11.1029.42","doi-asserted-by":"publisher","DOI":"10.1038\/ng0695-208"},{"key":"2021111810261540000_6.11.1029.43","first-page":"17","article-title":"Chromosome bands, their chromatin flavors, and their functional features.","volume":"51","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.44","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-298"},{"key":"2021111810261540000_6.11.1029.45","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-343"},{"key":"2021111810261540000_6.11.1029.46","doi-asserted-by":"crossref","first-page":"11394","DOI":"10.1016\/S0021-9258(18)60477-6","article-title":"Hypobetalipoproteinemia due to an apolipoprotein B gene exon 21 deletion derived by Alu-Alu recombination.","volume":"264","year":"1989","journal-title":"J. Biol. Chem."},{"key":"2021111810261540000_6.11.1029.47","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925562"},{"key":"2021111810261540000_6.11.1029.48","first-page":"441","article-title":"Founding BRCA1 mutations in hereditary breast and ovarian cancer in Southern Sweden.","volume":"58","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.49","unstructured":"Jurka, J. 1995. Origin and evolution of Alu repetitive elements. In Impact of short interspersed elements (SINEs) on the host genome (ed. RJ. Maraia), pp. 25\u201341. Landes Company, Austin, TX."},{"key":"2021111810261540000_6.11.1029.50","first-page":"1","article-title":"Breast cancer.","volume":"15","year":"1993","journal-title":"Epidemiol. Rev."},{"key":"2021111810261540000_6.11.1029.51","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90159-6"},{"key":"2021111810261540000_6.11.1029.52","doi-asserted-by":"crossref","first-page":"13581","DOI":"10.1016\/S0021-9258(18)67059-0","article-title":"Frameshift mutagenesis by eucaryotic DNA polymerases in vitro.","volume":"261","year":"1986","journal-title":"J. Biol. Chem."},{"key":"2021111810261540000_6.11.1029.53","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.15.5913"},{"key":"2021111810261540000_6.11.1029.54","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.21.2712"},{"key":"2021111810261540000_6.11.1029.55","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199601183340301"},{"key":"2021111810261540000_6.11.1029.56","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.11.3679"},{"key":"2021111810261540000_6.11.1029.57","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1016\/S0021-9258(18)61510-8","article-title":"Alu-Alu recombination deletes splice acceptor sites and produces secreted low density lipoprotein receptor in a subject with familial hypercholesteremia.","volume":"262","year":"1987","journal-title":"J. Biol. Chem."},{"key":"2021111810261540000_6.11.1029.58","first-page":"140","article-title":"Homologous recombination among three intragene Alu sequences causes an inversion-deletion resulting in the hereditary bleeding disorder Glanzmann thrombasthenia.","volume":"53","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.59","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(89)90311-5"},{"key":"2021111810261540000_6.11.1029.60","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-17"},{"key":"2021111810261540000_6.11.1029.61","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-439"},{"key":"2021111810261540000_6.11.1029.62","doi-asserted-by":"publisher","DOI":"10.1126\/science.7545954"},{"key":"2021111810261540000_6.11.1029.63","doi-asserted-by":"publisher","DOI":"10.1007\/BF00402152"},{"key":"2021111810261540000_6.11.1029.64","first-page":"6069","article-title":"Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds.","volume":"54","year":"1994","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.65","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.11.1919"},{"key":"2021111810261540000_6.11.1029.66","first-page":"33044","article-title":"Inheritance of human breast cancer: Evidence for autosomal dominant transmission in high-risk families.","volume":"85","year":"1988","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2021111810261540000_6.11.1029.67","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.22777"},{"key":"2021111810261540000_6.11.1029.68","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)83007-V"},{"key":"2021111810261540000_6.11.1029.69","first-page":"899","article-title":"Alu-Alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ehlers-Danlos syndrome.","volume":"55","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.70","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/7.2.203"},{"key":"2021111810261540000_6.11.1029.71","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5269.1755"},{"key":"2021111810261540000_6.11.1029.72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.2.256"},{"key":"2021111810261540000_6.11.1029.73","first-page":"1581","article-title":"Allele loss from chromosome 17 in ovarian cancer.","volume":"5","year":"1990","journal-title":"Oncogene"},{"key":"2021111810261540000_6.11.1029.74","first-page":"3382","article-title":"Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors.","volume":"53","year":"1993","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.75","first-page":"42","article-title":"A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families.","volume":"58","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2021111810261540000_6.11.1029.76","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520310033026"},{"key":"2021111810261540000_6.11.1029.77","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-392"},{"key":"2021111810261540000_6.11.1029.78","doi-asserted-by":"publisher","DOI":"10.1038\/ng1092-128"},{"key":"2021111810261540000_6.11.1029.79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1551"},{"key":"2021111810261540000_6.11.1029.80","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570102"},{"key":"2021111810261540000_6.11.1029.81","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/hmg\/4.suppl_1.1811","article-title":"Inherited breast and ovarian cancer.","volume":"4","year":"1995","journal-title":"Hum. Mol. Genet."},{"key":"2021111810261540000_6.11.1029.82","first-page":"2998","article-title":"Mutation analysis of the BRCA1 gene in ovarian cancers.","volume":"55","year":"1995","journal-title":"Cancer Res."},{"key":"2021111810261540000_6.11.1029.83","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.16.6463"},{"key":"2021111810261540000_6.11.1029.84","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-333"},{"key":"2021111810261540000_6.11.1029.85","doi-asserted-by":"publisher","DOI":"10.1038\/ng0495-444"},{"key":"2021111810261540000_6.11.1029.86","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90559-2"},{"key":"2021111810261540000_6.11.1029.87","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.18.8229"},{"key":"2021111810261540000_6.11.1029.88","first-page":"711","article-title":"BRCA1 expression is induced before DNA synthesis in both normal and tumor-derived breast cells.","volume":"7","year":"1996","journal-title":"Cell Growth Diff."},{"key":"2021111810261540000_6.11.1029.89","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.8.2160"},{"key":"2021111810261540000_6.11.1029.90","doi-asserted-by":"publisher","DOI":"10.1038\/368032a0"},{"key":"2021111810261540000_6.11.1029.91","first-page":"414","article-title":"High-throughput purification of M13 templates for DNA sequencing.","volume":"15","year":"1993","journal-title":"BioTechniques"},{"key":"2021111810261540000_6.11.1029.92","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(94)90041-8"},{"key":"2021111810261540000_6.11.1029.93","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.12.2259"},{"key":"2021111810261540000_6.11.1029.94","first-page":"241","article-title":"Recognizing exons in genomic sequence using GRAIL II.","volume":"16","year":"1994","journal-title":"Genet. Eng. N.Y."},{"key":"2021111810261540000_6.11.1029.95","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/ijc.2910540405","article-title":"Allelic loss in ovarian cancer.","volume":"54","year":"1993","journal-title":"Int. J. Cancer"}],"container-title":["Genome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gr.6.11.1029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T18:30:15Z","timestamp":1637260215000},"score":1,"resource":{"primary":{"URL":"http:\/\/genome.cshlp.org\/lookup\/doi\/10.1101\/gr.6.11.1029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,11]]},"references-count":95,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1996,11]]}},"alternative-id":["10.1101\/gr.6.11.1029"],"URL":"https:\/\/doi.org\/10.1101\/gr.6.11.1029","relation":{},"ISSN":["1088-9051"],"issn-type":[{"value":"1088-9051","type":"print"}],"subject":[],"published":{"date-parts":[[1996,11]]}}}